High-resolution silicon photonics focused ultrasound transducer with a sub-millimeter aperture.

We present an all-optical focused ultrasound transducer with a sub-millimeter aperture and demonstrate its capability for high-resolution imaging of tissue ex vivo. The transducer is composed of a wideband silicon photonics ultrasound detector and a miniature acoustic lens coated with a thin optically absorbing metallic layer used to produce laser-generated ultrasound. The demonstrated device achieves axial resolution and lateral resolutions of 12 µm and 60 µm, respectively, well below typical values achieved by conventional piezoelectric intravascular ultrasound. The size and resolution of the developed transducer may enable its use for intravascular imaging of thin fibrous cap atheroma.

Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination.

OBJECTIVES: The mRNA-based COVID-19 vaccines are now employed globally and have shown high efficacy in preventing SARS-CoV-2 infection. However, less is known about the vaccine efficacy in immune-suppressed individuals. This study sought to explore whether humoral immunity to the COVID-19 vaccine BNT162b2 is altered in RA patients treated with Janus kinase inhibitors by analysing their antibodies titre, neutralization activity and B cell responses. METHODS: We collected plasma samples from 12 RA patients who were treated with Janus kinase inhibitors and received two doses of the BNT162b2 vaccine, as well as 26 healthy individuals who were vaccinated with the same vaccine. We analysed the quantity of the anti-spike IgG and IgA antibodies that were elicited following the BNT162b2 vaccination, the plasma neutralization capacity and the responsiveness of the B-lymphocytes. We used ELISA to quantify the antibody titres, and a plasma neutralization assay was used to determine the virus neutralization capacity. Alteration in expression of the genes that are associated with B cell activation and the germinal centre response were analysed by quantitative PCR. RESULTS: Reduced levels of anti-spike IgG antibodies and neutralization capacity were seen in the RA patients who were treated with JAK inhibitors in comparison with healthy individuals. Furthermore, B cell responsiveness to the SARS-CoV-2 spike protein was reduced in the RA patients. CONCLUSION: RA patients who are treated with JAK inhibitors show a suppressed humoral response following BNT162b2 vaccination, as revealed by the quantity and quality of the anti-spike antibodies.

Burst-mode pulse interferometry for enabling low-noise multi-channel optical detection of ultrasound.

Ultrasound detection via optical resonators can achieve high levels of miniaturization and sensitivity as compared to piezoelectric detectors, but its scale-up from a single detector to an array is highly challenging. While the use of wideband sources may enable parallel interrogation of multiple resonators, it comes at the cost of reduction in the optical power, and ultimately in sensitivity, per channel. In this work we have developed a new interferometric approach to overcome this signal loss by using high-power bursts that are synchronized with the time window in which ultrasound detection is performed. Each burst is composed of a train of low-noise optical pulses which are sufficiently wideband to interrogate an array of resonators with non-overlapping spectra. We demonstrate our method, termed burst-mode pulse interferometry, for interrogating a single resonator in which the optical power was reduced to emulate the power loss per channel that occurs in parallel interrogation of 20 to 200 resonators. The use of bursts has led to up 25-fold improvement in sensitivity without affecting the shape of the acoustic signals, potentially enabling parallel low-noise interrogation of resonator arrays with a single source.

Miniaturized ultrasound detector arrays in silicon photonics using pulse transmission amplitude monitoring.

Silicon photonics holds promise for a new generation of ultrasound-detection technology, based on optical resonators, with unparalleled miniaturization levels, sensitivities, and bandwidths, creating new possibilities for minimally invasive medical devices. While existing fabrication technologies are capable of producing dense resonator arrays whose resonance frequency is pressure sensitive, simultaneously monitoring the ultrasound-induced frequency modulation of numerous resonators has remained a challenge. Conventional techniques, which are based on tuning a continuous wave laser to the resonator wavelength, are not scalable due to the wavelength disparity between the resonators, requiring a separate laser for each resonator. In this work, we show that the Q-factor and transmission peak of silicon-based resonators can also be pressure sensitive, exploit this phenomenon to develop a readout scheme based on monitoring the amplitude, rather than frequency, at the output of the resonators using a single-pulse source, and demonstrate its compatibility with optoacoustic tomography.

Simultaneous multi-channel ultrasound detection via phase modulated pulse interferometry.

In optical detection of ultrasound, resonators with high Q-factors are often used to maximize sensitivity. However, in order to perform parallel interrogation, conventional interferometric techniques require an overlap between the spectra of all the resonators, which is difficult to achieve with high Q-factor resonators. In this paper, a new method is developed for parallel interrogation of optical resonators with non-overlapping spectra. The method is based on a phase-modulation scheme for pulse interferometry (PM-PI) and requires only a single photodetector and sampling channel per ultrasound detector. Using PM-PI, parallel ultrasound detection is demonstrated with four high Q-factor resonators.

Ultrasound detection via low-noise pulse interferometry using a free-space Fabry-Pérot.

Coherence-restored pulse interferometry (CRPI) is a recently developed method for optical detection of ultrasound that achieves shot-noise-limited sensitivity and high dynamic range. In principle, the wideband source employed in CRPI may enable the interrogation of multiple detectors by using wavelength multiplexing. However, the noise-reduction scheme in CRPI has not been shown to be compatible with wideband operation. In this work, we introduce a new scheme for CRPI that relies on a free-space Fabry-Pérot filter for noise reduction and a pulse stretcher for reducing nonlinear effects. Using our scheme, we demonstrate that shot-noise-limited detection may be achieved for a spectral band of 80 nm and powers of up to 5 mW.

Passive-demodulation pulse interferometry for ultrasound detection with a high dynamic range.

In the optical detection of ultrasound, resonators with high Q-factors are often used to maximize sensitivity. However, increasing the Q-factor of a resonator may reduce the linear range of the interrogation scheme, making it more susceptible to strong external perturbations and incapable of measuring strong acoustic signals. In this Letter, a passive-demodulation scheme for pulse interferometry was developed for high dynamic-range measurements. The passive scheme was based on an unbalanced Mach-Zehnder interferometer and a 90° optical hybrid, which was implemented in a dual-polarization all-fiber setup. We demonstrated the passive scheme for detecting ultrasound bursts with pressure levels for which the response of conventional, active interferometric techniques became nonlinear.

Accelerating Self-Imaging: The Airy-Talbot Effect.

We present a new type of self-imaging phenomenon: self-imaging along curved trajectories. Unlike the Talbot effect, where self-imaging occurs for periodic wave patterns propagating along a straight line, here the field is generally not periodic and is self-imaged along curved trajectories. In the paraxial regime, self-imaging along a parabolic trajectory can ideally go on indefinitely. In the nonparaxial regime the self-imaging is along a circular trajectory and lasts as long as the beam bends. We demonstrate this accelerating self-imaging effect experimentally, and discuss generalizations to higher dimensions.

All-optical optoacoustic micro-tomography in reflection mode.

High-resolution optoacoustic imaging at depths beyond the optical diffusion limit is conventionally performed using a microscopy setup where a strongly focused ultrasound transducer samples the image object point-by-point. Although recent advancements in miniaturized ultrasound detectors enables one to achieve microscopic resolution with an unfocused detector in a tomographic configuration, such an approach requires illuminating the entire object, leading to an inefficient use of the optical power, and imposing a trans-illumination configuration that is limited to thin objects. We developed an optoacoustic micro-tomography system in an epi-illumination configuration, in which the illumination is scanned with the detector. The system is demonstrated in phantoms for imaging depths of up to 5 mm and in vivo for imaging the vasculature of a mouse ear. Although image-formation in optoacoustic tomography generally requires static illumination, our numerical simulations and experimental measurements show that this requirement is relaxed in practice due to light diffusion, which homogenizes the fluence in deep tissue layers.

Homodyne time-of-flight acousto-optic imaging for low-gain photodetector.

Acousto-optics imaging (AOI) is a hybrid imaging modality that is capable of mapping the light fluence rate in deep tissue by local ultrasound modulation of the diffused photons. Since the intensity of the modulated photons is relatively low, AOI systems often rely on high-gain photodetectors, e.g. photomultiplier tubes (PMTs), which limit scalability due to size and cost and may significantly increase the relative shot-noise in the detected signal due to low quantum yields or gain noise. In this work, we have developed a homodyne AOI scheme in which the modulated photons are amplified by interference with a reference beam, enabling their detection with a single low-gain photodetector in reflection-mode configuration. We experimentally demonstrate our approach with a silicon photodiode, achieving over a 4-fold improvement in SNR in comparison to a PMT-based setup. The increased SNR manifested in lower background noise level thus enabling deeper imaging depths. The use of a fiber-based configuration enables the integration of our scheme in a hand-held AOI probe.

Silicon photonic acoustic detector (SPADE) using a silicon nitride microring resonator.

Silicon photonics is an emerging platform for acoustic sensing, offering exceptional miniaturization and sensitivity. While efforts have focused on silicon-based resonators, silicon nitride resonators can potentially achieve higher Q-factors, further enhancing sensitivity. In this work, a 30 µm silicon nitride microring resonator was fabricated and coated with an elastomer to optimize acoustic sensitivity and signal fidelity. The resonator was characterized acoustically, and its capability for optoacoustic tomography was demonstrated. An acoustic bandwidth of 120 MHz and a noise-equivalent pressure of ∼ 7 mPa/Hz1/2 were demonstrated. The spatially dependent impulse response agreed with theoretical predictions, and spurious acoustic signals, such as reverberations and surface acoustic waves, had a marginal impact. High image fidelity optoacoustic tomography of a 20 µm knot was achieved, confirming the detector's imaging capabilities. The results show that silicon nitride offers low signal distortion and high-resolution optoacoustic imaging, proving its versatility for acoustic imaging applications.

Silicon-photonics acoustic detector for optoacoustic micro-tomography.

Medical ultrasound and optoacoustic (photoacoustic) imaging commonly rely on the concepts of beam-forming and tomography for image formation, enabled by piezoelectric array transducers whose element size is comparable to the desired resolution. However, the tomographic measurement of acoustic signals becomes increasingly impractical for resolutions beyond 100 µm due to the reduced efficiency of piezoelectric elements upon miniaturization. For higher resolutions, a microscopy approach is preferred, in which a single focused ultrasound transducer images the object point-by-point, but the bulky apparatus and long acquisition time of this approach limit clinical applications. In this work, we demonstrate a miniaturized acoustic detector capable of tomographic imaging with spread functions whose width is below 20 µm. The detector is based on an optical resonator fabricated in a silicon-photonics platform coated by a sensitivity-enhancing elastomer, which also effectively eliminates the parasitic effect of surface acoustic waves. The detector is demonstrated in vivo in high-resolution optoacoustic tomography.

Silicon-photonics focused ultrasound detector for minimally invasive optoacoustic imaging.

One of the main challenges in miniaturizing optoacoustic technology is the low sensitivity of sub-millimeter piezoelectric ultrasound transducers, which is often insufficient for detecting weak optoacoustic signals. Optical detectors of ultrasound can achieve significantly higher sensitivities than their piezoelectric counterparts for a given sensing area but generally lack acoustic focusing, which is essential in many minimally invasive imaging configurations. In this work, we develop a focused sub-millimeter ultrasound detector composed of a silicon-photonics optical resonator and a micro-machined acoustic lens. The acoustic lens provides acoustic focusing, which, in addition to increasing the lateral resolution, also enhances the signal. The developed detector has a wide bandwidth of 84 MHz, a focal width smaller than 50 µm, and noise-equivalent pressure of 37 mPa/Hz1/2 - an order of magnitude improvement over conventional intravascular ultrasound. We show the feasibility of the approach and the detector's imaging capabilities by performing high-resolution optoacoustic microscopy of optical phantoms with complex geometries.

Single pixel imaging at megahertz switching rates via cyclic Hadamard masks.

Optical imaging is commonly performed with either a camera and wide-field illumination or with a single detector and a scanning collimated beam; unfortunately, these options do not exist at all wavelengths. Single-pixel imaging offers an alternative that can be performed with a single detector and wide-field illumination, potentially enabling imaging applications in which the detection and illumination technologies are immature. However, single-pixel imaging currently suffers from low imaging rates owing to its reliance on configurable spatial light modulators, generally limited to 22 kHz rates. We develop an approach for rapid single-pixel imaging which relies on cyclic patterns coded onto a spinning mask and demonstrate it for in vivo imaging of C. elegans worms. Spatial modulation rates of up to 2.4 MHz, imaging rates of up to 72 fps, and image-reconstruction times of down to 1.5 ms are reported, enabling real-time visualization of dynamic objects.